Up-regulation of tumor necrosis factor-alpha and interferon-gamma expression in the spleen and lungs of mice infected with the human Babesia isolate WA1.

We analyzed cytokine expression in mice infected with the intraerythrocytic parasites Babesia microti and WA1. In C3H/HeN mice, WA1 infections were fatal, whereas B. microti infections were resolved. We propose that the proinflammatory cytokines tumor necrosis factor-alpha (TNFalpha) and interferon-gamma (IFNgamma) contribute to the WA1-associated disease. WA1 infection was characterized by up-regulation of TNFalpha and IFNgamma mRNA in the spleen. Previous studies in WA1-infected mice showed that pathologic lesions occurred primarily in the lungs, including pulmonary edema and intravascular margination of leukocytes. Analysis of cytokine expression in the lungs is important for an understanding of the disease process in WA1-infected mice. Expression of both TNFalpha and IFNgamma mRNA was increased in the lungs of WA1-infected mice. Immunohistochemical staining confirmed the upregulation of these proinflammatory cytokines in the lungs. Expression of TNFalpha and IFNgamma was not up-regulated in the lungs of B. microti-infected mice. The results implicate TNFalpha and IFNgamma in the pathogenesis of WA1-associated disease.